Taste has profound effects on smoking behavior. Most importantly, smokers of flavored cigarette have higher odds for relapse. Gustatory and other visceral sensory information are processed and integrated in the insular cortex. Damaging of insular cortex in stroke patients resulted in immediate quitting of smoking, without relapse, and without persistence of the urge to smoke. Therefore, the first aim of this proposal is to establish an adolescent animal model of i.v. nicotine self-administration using licking as the operant behavior and a novel taste as the conditioned stimulus. In the second aim, we will test the hypothesis that gustatory, audio and visual cues activate common subregions of the insular cortex during reinstatement of nicotine seeking behavior. This proposal is suited for the CEBRA program not only because it aims to establish an innovative drug SA model that incorporates contingent gustatory cue, but, more importantly, because it tests a highly novel and significant hypothesis, which there is scant precedent or preliminary data. If confirmed, this would have a substantial impact on current thinking of the brain circuitry involved in relapse to drug abuse. PUBLIC HEALTH RELEVANCE: Relapse is a major problem in treating nicotine addiction. An animal model of voluntary nicotine consumption with a taste cue will be established to explore the role of insular cortex in relapse to smoking.